Late Morbidity and Mortality After Autologous Blood or Marrow Transplantation in Children, Adolescents, and Young Adults With Lymphoma

High-dose chemotherapy (HDC) with autologous hematopoietic cell transplant (HCT) is a critical intervention for children and adolescents/young adults (AYAs) with relapsed or refractory Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). The few existing studies of long-term morbidity and mortality after HCT for HL and NHL are limited by the scarcity of pediatric data, small sample size, or comparatively short follow-up. Survivorship care of individuals with a history of lymphoma treated with HDC and HCT requires a detailed understanding of disease-, treatment-, and patient-specific late morbidity and mortality.

Holmqvist and colleagues recently published data from the Blood or Bone Marrow Transplant Survivor Study (BMTSS) that described late morbidity and mortality in 583 pediatric and AYA lymphoma survivors who underwent HCT. This study included pediatric (14.4%; n = 84) and young adult (85.6%; n = 499) patients who received an autologous HCT before age 40 years and survived at least 2 years after the transplant. The median follow-up was 9.8 years (2.0–32.1). The control for this study was a group of siblings of HCT recipients who were enrolled in BMTSS; 16% of the HCT survivors in this study were related to the siblings included in the control group. The authors used an extensive, validated survey tool and found that HL and NHL survivors who underwent HCT were at a threefold higher risk (95% CI, 2.3–4.1) for CTCAE v5.0 grade 3 to 4 chronic health conditions compared with controls. The 20-year cumulative incidence of any grade 3 to 5 chronic health conditions for the entire cohort was 47.1%. The most common grade 3 to 5 chronic health conditions in HCT survivors were subsequent malignant neoplasms (11.6%) and cardiovascular disease (10.5%). The all-cause mortality rate at 25 years was 62.6% for HL and 42.3% for NHL. Relapse-related mortality (RRM) plateaued after 20 years post HCT. Nonrelapse mortality (NRM) crossed RRM after 20 years. Common causes of death included primary malignancy (35%), infection (22%), subsequent malignancy (16%), cardiovascular disease (13%), pulmonary disease (4%), and homicide/suicide/accident (4%). Groups with higher all-cause mortality included individuals with HL (compared with those with NHL), Black individuals, Hispanic individuals, and those with an income of less than $75,000 at the time of the survey.

The study by Holmqvist et al adds to our understanding of lymphoma transplant survivorship due, in part, to its inclusion of pediatric patients, large sample size, and long follow-up. There are several key findings. First, survivors are at higher risk of severe chronic health conditions, including secondary neoplasms and cardiovascular disease. Second, the burden of RRM persists decades after the transplant. Third, subpopulations with worse outcomes included Black and Hispanic individuals and those with lower socioeconomic status. We agree with the conclusions of the authors — this study demonstrates a clear need for long-term follow-up with a focus on vulnerable populations.